The overall objective of the Neuropathology Core of the University of Kentucky Alzheimer's Disease Center is to support research on normal brain aging, presymptomatic Alzheimer's disease (AD), mild cognitive impairment (MCI), early and late AD, mixed dementia syndromes, and other dementing disorders. The core will perform short postmortem interval (2-4 hr) autopsies by our Rapid Autopsy Team on longitudinally followed subjects from our normal control BRAiNS Clinic, Dementia Research Clinic, and Kentucky Clinic North Minority Satellite (KYCN), and provide brain specimens, CSF and synaptosomes for investigators at UK, other ADCs, and outside investigators. The core will also provide consensus conference determined diagnoses, quantitation of neurofibrillary tangles (NFT), neuritic plaques, and diffuse plaques from 8 brain regions, Abeta 1-40 and 1-42 quantitation, Braak staging, CERAD, and NIA-Reagan Institute staging on all autopsied cases to investigators. The core will maintain a tissue bank of the above specimens and frozen serum, plasma, buffy coats and CSF from living patients from the Dementia Research Clinic, the normal control BRAiNS Clinic, and KYCN. Special emphasis will be placed on defining the neuropathological findings in the brains of the oldest old (>85), and providing investigators with specimens from cognitively normal control subjects with no Abeta and few NFT (Braak O-ll) (successful cerebral aging) and cognitively normal control subjects with abundant Abeta and NFT. Monthly or more frequent consensus conferences will be held with the Clinical Core to define clinical-pathological diagnoses on all autopsied subjects. Clinical-pathological conferences will be held every two months and twice annually for the Ohio Valley Geriatric Research Center. Support for the Nun Study, the Honolulu Asian Aging study, the UK Udall Parkinson's Disease Research Center and the Georgia Centenarian Study will be provided by the Neuropathology Core. This core's unique opportunity to conduct clinical-pathological correlative studies on longitudinally followed subjects to better understand normal brain aging and the transition to dementia and the factors involved in this transition, could contribute to early interventions and possible preventive measures.